{"title":"磁性氧化石墨烯衍生物中As2O3的合成和表征:在角质形成细胞和黑色素瘤细胞中的生物活性","authors":"Altevir Rossato Viana , Alice Penteado Holkem , Franciele da Silva Bruckmann , Nickolas Pippi , Leonardo Vidal Zancanaro , Sergio Roberto Mortari , Erico Marlon Moraes Flores , Cristiano Rodrigo Bohn Rhoden , André Passaglia Schuch","doi":"10.1016/j.jddst.2025.107023","DOIUrl":null,"url":null,"abstract":"<div><div>Cancer is the second leading cause of death worldwide, and melanoma is the type of skin tumor with the worst prognosis. Traditional oncology treatments cause numerous adverse effects, as they affect proliferating cells throughout the body. Therefore, this study evaluated the chemical synthesis and biological activity of the chemotherapeutic drug Arsenic Trioxide (As<sub>2</sub>O<sub>3</sub>), incorporated into graphene oxide (GO) containing different amounts of magnetite (Fe<sub>3</sub>O<sub>4</sub>) covering its surface (1:1 and 1:10). XRD, FTIR, SEM, and EDS techniques were performed to characterize GO·Fe<sub>3</sub>O<sub>4</sub>-As<sub>2</sub>O<sub>3</sub>. Initially, the IC50 was determined in B16-F10 (melanoma) and HaCat (keratinocytes) cell lines using the MTT assay for all treatments, which had a concentration range between 10 and 300 μg mL<sup>−1</sup>, and subsequently, dsDNA PicoGreen, Colony Formation, DCFH-DA, NO, and Superoxide were evaluted. Experimental data showed that the synthesized material contained complexed As<sub>2</sub>O<sub>3</sub>. Regarding the biological assays, free As<sub>2</sub>O<sub>3</sub> was toxic to the tested cells; however, the most significant IC<sub>50</sub> results were 557 μg mL<sup>−1</sup> and 75 μg mL<sup>−1</sup> for HaCat and B16-F10, respectively, in the treatment with (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub>. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub> in non-tumor cells. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub> in non-tumor cells. ROS production was generally significant only at higher concentrations containing As<sub>2</sub>O<sub>3</sub>, while none of these treatments elevated NO levels remained unaffected. Superoxide levels were significantly elevated compared to the untreated control. These findings suggest that GO·Fe<sub>3</sub>O<sub>4</sub>-As<sub>2</sub>O<sub>3</sub> nanocomposites hold promise as a targeted therapeutic approach for melanoma, offering improved cytotoxic selectivity and potential for further biomedical applications.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"109 ","pages":"Article 107023"},"PeriodicalIF":4.5000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and characterization of As2O3 incorporated into magnetic graphene oxide derivatives: Biological activity in keratinocytes and melanoma cells\",\"authors\":\"Altevir Rossato Viana , Alice Penteado Holkem , Franciele da Silva Bruckmann , Nickolas Pippi , Leonardo Vidal Zancanaro , Sergio Roberto Mortari , Erico Marlon Moraes Flores , Cristiano Rodrigo Bohn Rhoden , André Passaglia Schuch\",\"doi\":\"10.1016/j.jddst.2025.107023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Cancer is the second leading cause of death worldwide, and melanoma is the type of skin tumor with the worst prognosis. Traditional oncology treatments cause numerous adverse effects, as they affect proliferating cells throughout the body. Therefore, this study evaluated the chemical synthesis and biological activity of the chemotherapeutic drug Arsenic Trioxide (As<sub>2</sub>O<sub>3</sub>), incorporated into graphene oxide (GO) containing different amounts of magnetite (Fe<sub>3</sub>O<sub>4</sub>) covering its surface (1:1 and 1:10). XRD, FTIR, SEM, and EDS techniques were performed to characterize GO·Fe<sub>3</sub>O<sub>4</sub>-As<sub>2</sub>O<sub>3</sub>. Initially, the IC50 was determined in B16-F10 (melanoma) and HaCat (keratinocytes) cell lines using the MTT assay for all treatments, which had a concentration range between 10 and 300 μg mL<sup>−1</sup>, and subsequently, dsDNA PicoGreen, Colony Formation, DCFH-DA, NO, and Superoxide were evaluted. Experimental data showed that the synthesized material contained complexed As<sub>2</sub>O<sub>3</sub>. Regarding the biological assays, free As<sub>2</sub>O<sub>3</sub> was toxic to the tested cells; however, the most significant IC<sub>50</sub> results were 557 μg mL<sup>−1</sup> and 75 μg mL<sup>−1</sup> for HaCat and B16-F10, respectively, in the treatment with (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub>. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub> in non-tumor cells. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe<sub>3</sub>O<sub>4</sub> 1:1)-As<sub>2</sub>O<sub>3</sub> in non-tumor cells. ROS production was generally significant only at higher concentrations containing As<sub>2</sub>O<sub>3</sub>, while none of these treatments elevated NO levels remained unaffected. Superoxide levels were significantly elevated compared to the untreated control. These findings suggest that GO·Fe<sub>3</sub>O<sub>4</sub>-As<sub>2</sub>O<sub>3</sub> nanocomposites hold promise as a targeted therapeutic approach for melanoma, offering improved cytotoxic selectivity and potential for further biomedical applications.</div></div>\",\"PeriodicalId\":15600,\"journal\":{\"name\":\"Journal of Drug Delivery Science and Technology\",\"volume\":\"109 \",\"pages\":\"Article 107023\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Delivery Science and Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1773224725004265\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Delivery Science and Technology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1773224725004265","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
癌症是全球第二大死因,而黑色素瘤是预后最差的一种皮肤肿瘤。传统的肿瘤治疗会导致许多副作用,因为它们会影响全身的增殖细胞。因此,本研究评估了化疗药物三氧化二砷(As2O3)的化学合成和生物活性,将其掺入含有不同数量的磁铁矿(Fe3O4)覆盖其表面(1:1和1:10)的氧化石墨烯(GO)。采用XRD、FTIR、SEM、EDS等技术对氧化石墨烯·Fe3O4-As2O3进行表征。首先,使用MTT法测定B16-F10(黑色素瘤)和HaCat(角质形成细胞)细胞系的IC50,浓度范围在10至300 μg mL−1之间,随后评估dsDNA PicoGreen、菌落形成、DCFH-DA、NO和超氧化物。实验数据表明,合成的材料中含有络合的As2O3。在生物实验方面,游离As2O3对被试细胞有毒性;在(GO·Fe3O4 1:1)-As2O3处理下,HaCat和B16-F10的IC50值分别为557 μg mL - 1和75 μg mL - 1。除在非肿瘤细胞中(GO·Fe3O4 1:1)-As2O3外,抗增殖活性结果也显示集落形成明显减少。除在非肿瘤细胞中(GO·Fe3O4 1:1)-As2O3外,抗增殖活性结果也显示集落形成明显减少。一般来说,只有在含有较高浓度As2O3的情况下,ROS的产生才会显著,而这些处理都不会影响NO水平的升高。与未经治疗的对照组相比,超氧化物水平显著升高。这些发现表明,氧化石墨烯·Fe3O4-As2O3纳米复合材料有望作为黑色素瘤的靶向治疗方法,提供更好的细胞毒性选择性和进一步的生物医学应用潜力。
Synthesis and characterization of As2O3 incorporated into magnetic graphene oxide derivatives: Biological activity in keratinocytes and melanoma cells
Cancer is the second leading cause of death worldwide, and melanoma is the type of skin tumor with the worst prognosis. Traditional oncology treatments cause numerous adverse effects, as they affect proliferating cells throughout the body. Therefore, this study evaluated the chemical synthesis and biological activity of the chemotherapeutic drug Arsenic Trioxide (As2O3), incorporated into graphene oxide (GO) containing different amounts of magnetite (Fe3O4) covering its surface (1:1 and 1:10). XRD, FTIR, SEM, and EDS techniques were performed to characterize GO·Fe3O4-As2O3. Initially, the IC50 was determined in B16-F10 (melanoma) and HaCat (keratinocytes) cell lines using the MTT assay for all treatments, which had a concentration range between 10 and 300 μg mL−1, and subsequently, dsDNA PicoGreen, Colony Formation, DCFH-DA, NO, and Superoxide were evaluted. Experimental data showed that the synthesized material contained complexed As2O3. Regarding the biological assays, free As2O3 was toxic to the tested cells; however, the most significant IC50 results were 557 μg mL−1 and 75 μg mL−1 for HaCat and B16-F10, respectively, in the treatment with (GO·Fe3O4 1:1)-As2O3. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe3O4 1:1)-As2O3 in non-tumor cells. The antiproliferative activity results also showed a strong decrease in colony formation, except for (GO·Fe3O4 1:1)-As2O3 in non-tumor cells. ROS production was generally significant only at higher concentrations containing As2O3, while none of these treatments elevated NO levels remained unaffected. Superoxide levels were significantly elevated compared to the untreated control. These findings suggest that GO·Fe3O4-As2O3 nanocomposites hold promise as a targeted therapeutic approach for melanoma, offering improved cytotoxic selectivity and potential for further biomedical applications.
期刊介绍:
The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.